Four dead canine pups (5-12 days old) from 3 litters in Douglas County of north central Colorado were submitted to the Colorado State University Diagnostic Laboratory for necropsy. Pups were originally presented to the referring clinics for respiratory tract illness, with or without diarrhea. At necropsy, the lungs from all pups had similar lesions, including random foci of hemorrhage and failure to collapse on opening of the thoracic cavity. The lungs were histologically characterized by subacute interstitial pneumonia, with alveolar septa expanded by a histiocyte-rich infiltrate with a few lymphocytes and neutrophils. The alveolar spaces were filled with moderate amounts of proteinaceous fluid, foamy macrophages, and a few neutrophils. Lungs from 3 of the 4 pups were test positive for canine distemper virus (CDV) by use of reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Immunohistochemically stained lungs, including those from the pup that were CDV negative, by use of RT-PCR analysis, were test positive for CDV antigen in bronchial and bronchiolar epithelial cells and in a few alveolar macrophages. Central nervous system lesions were not observed in any of the 4 pups. These cases represent an unusual presentation of canine distemper in neonatal pups marked by respiratory tract lesions without central nervous system involvement. Canine distemper should be considered in the differential diagnosis of neonatal canine respiratory tract illness.